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1.
J Am Chem Soc ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177513

RESUMO

Lead halide perovskites have attracted significant attention for their wide-ranging applications in optoelectronic devices. A ubiquitous element in these applications is that charging of the perovskite is involved, which can trigger electrochemical degradation reactions. Understanding the underlying factors governing these degradation processes is crucial for improving the stability of perovskite-based devices. For bulk semiconductors, the electrochemical decomposition potentials depend on the stabilization of atoms in the lattice-a parameter linked to the material's solubility. For perovskite nanocrystals (NCs), electrochemical surface reactions are strongly influenced by the binding equilibrium of passivating ligands. Here, we report a spectro-electrochemical study on CsPbBr3 NCs and bulk thin films in contact with various electrolytes, aimed at understanding the factors that control cathodic degradation. These measurements reveal that the cathodic decomposition of NCs is primarily determined by the solubility of surface ligands, with diminished cathodic degradation for NCs in high-polarity electrolyte solvents where ligand solubilities are lower. However, the solubility of the surface ligands and bulk lattice of NCs are orthogonal, such that no electrolyte could be identified where both the surface and bulk are stabilized against cathodic decomposition. This poses inherent challenges for electrochemical applications: (i) The electrochemical stability window of CsPbBr3 NCs is constrained by the reduction potential of dissolved Pb2+ complexes, and (ii) cathodic decomposition occurs well before the conduction band can be populated with electrons. Our findings provide insights to enhance the electrochemical stability of perovskite thin films and NCs, emphasizing the importance of a combined selection of surface passivation and electrolyte.

2.
J Prev Alzheimers Dis ; 11(4): 917-927, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39044503

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intricate genetic and environmental etiology. The objective of this study was to identify robust non-genetic risk factors for AD through an updated umbrella review. METHODS: We conducted a comprehensive search of meta-analyses and systematic reviews on non-genetic risk factors associated with AD in PubMed, Cochrane, Embase, and Ovid Medline up to June 30, 2023. After collecting data, we estimated the summary effect size and their 95% confidence intervals. The degree of heterogeneity between studies was assessed using I2 statistics and a 95% prediction interval was determined. Additionally, we evaluated potential excess significant bias and small study effects within the selected candidate studies. RESULTS: The umbrella review encompassed a total of 53 eligible papers, which included 84 meta-analyses covering various factors such as lifestyle, diet, environmental exposures, comorbidity or infections, drugs, and biomarkers. Based on the evidence classification criteria employed in this study, two factors as convincing evidence (Class I), including rheumatoid arthritis (RA), potentially reduced the risk of AD, but diabetes significantly increased the risk of AD. Furthermore, three factors as highly suggestive evidence (Class II), namely depression, high homocysteine, and low folic acid level, potentially increased the risk of AD. CONCLUSION: Our findings highlight several risk factors associated with AD that warrant consideration as potential targets for intervention. However, it is crucial to prioritize the identified modifiable risk factors, namely rheumatoid arthritis, diabetes, depression, elevated homocysteine levels, and low folic acid levels to effectively address this complex neurodegenerative disorder.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/genética , Doença de Alzheimer/epidemiologia , Humanos , Fatores de Risco , Artrite Reumatoide/genética , Biomarcadores/sangue , Estilo de Vida
3.
ACS Nano ; 18(22): 14685-14695, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38773944

RESUMO

Indium phosphide (InP) quantum dots (QDs) are considered the most promising alternative for Cd and Pb-based QDs for lighting and display applications. However, while core-only QDs of CdSe and CdTe have been prepared with near-unity photoluminescence quantum yield (PLQY), this is not yet achieved for InP QDs. Treatments with HF have been used to boost the PLQY of InP core-only QDs up to 85%. However, HF etches the QDs, causing loss of material and broadening of the optical features. Here, we present a simple postsynthesis HF-free treatment that is based on passivating the surface of the InP QDs with InF3. For optimized conditions, this results in a PLQY as high as 93% and nearly monoexponential photoluminescence decay. Etching of the particle surface is entirely avoided if the treatment is performed under stringent acid-free conditions. We show that this treatment is applicable to InP QDs with various sizes and InP QDs obtained via different synthesis routes. The optical properties of the resulting core-only InP QDs are on par with InP/ZnSe/ZnS core-shell QDs, with significantly higher absorption coefficients in the blue, and with potential for faster charge transport. These are important advantages when considering InP QDs for use in micro-LEDs or photodetectors.

4.
5.
J Am Chem Soc ; 146(14): 9928-9938, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38530865

RESUMO

The optoelectronic properties of colloidal quantum dots (cQDs) depend critically on the absolute energy of the conduction and valence band edges. It is well known these band-edge energies are sensitive to the ligands on the cQD surface, but it is much less clear how they depend on other experimental conditions, like solvation. Here, we experimentally determine the band-edge positions of thin films of PbS and ZnO cQDs via spectroelectrochemical measurements. To achieve this, we first carefully evaluate and optimize the electrochemical injection of electrons and holes into PbS cQDs. This results in electrochemically fully reversible electron injection with >8 electrons per PbS cQDs, allowing the quantitative determination of the conduction band energy for PbS cQDs with various diameters and surface compositions. Surprisingly, we find that the band-edge energies shift by nearly 1 eV in the presence of different solvents, a result that also holds true for ZnO cQDs. We argue that complexation and partial charge transfer between solvent and surface ions are responsible for this large effect of the solvent on the band-edge energy. The trend in the energy shift matches the results of density functional theory (DFT) calculations in explicit solvents and scales with the energy of complexation between surface cations and solvents. As a first approximation, the solvent Lewis basicity can be used as a good descriptor to predict the shift of the conduction and valence band edges of solvated cQDs.

6.
Zhonghua Xue Ye Xue Za Zhi ; 45(1): 68-73, 2024 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-38527841

RESUMO

Objective: To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) . Methods: The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups. Results: The baseline parameters were balanced between the two groups (P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant (P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups (P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% (P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) (P=0.198) . Conclusion: The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.


Assuntos
Anemia Aplástica , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Animais , Coelhos , Humanos , Anemia Aplástica/tratamento farmacológico , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Ciclofosfamida
8.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 58(11): 1103-1110, 2023 Oct 26.
Artigo em Chinês | MEDLINE | ID: mdl-37885180

RESUMO

Objective: Cone-beam CT (CBCT) images were used to investigate the relative position changes of mandibular foramen in the mandible of children and the relative position relationship with the occlusal plane, so as to provide clinical guidance for inferior alveolar nerve block (IANB) anesthesia of children. Methods: The CBCT data of 202 children aged 7-10 years in the image database of the First Affiliated Hospital of Zhengzhou University from March 2021 to February 2023 were included. Patients were divided into 4 groups according to age diffrences as 7-year-old, 8-year-old, 9-year-old and 10-year-old. There were 20 males and 22 females in the 7-year-old group, 31 males and 28 females in the 8-year-old group, 30 males and 26 females in the 9-year-old group, and 22 males and 23 females in the 10-year-old group, respectively. Forty-six adults aged 25-30 years were selected as control group, 24 males and 22 females included. The distance between the center point of mandibular foramen with the anterior edge of ascending ramus of mandible (MF-A), the posterior edge of the ascending ramus of mandible (MF-P) and the shortest distance between the center point of mandibular foramen with occlusal plane (MF-OP) were measured. The angle between the center point of the mandibular foramen with the sagittal plane of the mandibular first deciduous molar (or mandibular first premolar) and mandibular second deciduous molar (or mandibular second premolar) (∠A) was measured. The data of mandibular foramen were compared between the left and right sides and among different genders and different age groups. Results: The position of mandibular foramen in children aged 7-10 years maintained bilateral symmetry, and mandibular growth and development were relatively consistent between different genders (P>0.05). MF-A increased with age, from (15.83±1.28) mm in 7-year-old group to (17.10±1.60) mm in 10-year-old group gradually. There were significant differences in MF-A between the 10-year-old group with the 7-year-old group, the 8-year-old group [(15.98±1.53) mm] and the 9-year-old group [(16.43±1.49) mm] respectively (P<0.05). MF-P increased with age, from (9.12±1.17) mm in 7-year-old group to (11.25±1.60) mm in 10-year-old group. There were statistically significant differences in MF-P among all age groups (P<0.05). MF-OP increased with age, from below the plane (-0.24±2.31) mm in the 7-year-old group to above the plane (1.08±1.95) mm in the 10-year-old group. There were significant differences between the 10-year-old group with the 7-year-old group, the 8-year-old group [(-0.01±1.93) mm], and the 9-year-old group [(0.31±1.95) mm] (P<0.05). The ratio of MF-A to MF-P decreased as the age increased, from 1.77±0.30 in the 7-year-old group to 1.55±0.29 in the 10-year-old group. There were statistically significant differences in MF-A/MF-P among all age groups (P<0.05), except for between the 8-year-old group (1.66±0.19) and the 9-year-old group (1.65±0.28) (P>0.05). The ∠A of children in all age groups was significantly greater than the reference value (45°) (P<0.05), and there was no statistical significance among all groups (P>0.05). The differences of MF-A, MF-P, MF-OP, MF-A/MF-P and ∠A between children of all age groups and the control group were statistically significant (P<0.05). Conclusions: In children aged 7-10 years, the mandibular foramen is located behind the midpoint of the anteroposterior diameter of the mandibular ramus. With the increase of age, the mandibular foramen gradually moves from below the occlusal plane to above, and is flush with the occlusal plane at the age of 8 years. Compared with adults, the mandibular foramen in children is more backward and lower on the medial side of the mandibular ramus. When IANB is operated to children, the syringe can be moved distally from the contact area of the contralateral deciduous molars or premolars, so that the injection angle can be greater than the reference value 45° to improve the accuracy of IANB.

9.
Eur Rev Med Pharmacol Sci ; 27(16): 7470-7484, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37667923

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA), as an autoimmune disease, poses a huge social and economic burden worldwide. Although the diagnosis of RA has been gradually improved, there is still a need to discover accurate and rapid biomarkers for diagnosis and therapy with a precise understanding of the disease. This study aimed to screen diagnostic biomarkers and analyze immune infiltration in RA based on weighted gene co-expression network analysis (WGCNA). MATERIALS AND METHODS: Firstly, we screened the experimental and validation sets associated with RA from the GEO database. Crossover genes were obtained using differential genes (DEGs) and key modules in WGCNA. Subsequently, the crossover genes were constructed into protein-protein interaction (PPI) networks and screened to obtain hub genes. The receiver operating characteristic (ROC) curve assessment was performed to identify diagnostic biomarkers. In addition, we used the Cibersort algorithm for immuno-infiltration analysis and the DGidb database to search for drugs associated with diagnostic biomarkers. RESULTS: In the end, 377 DEGs were identified, and the enrichment analysis revealed significant associations with the immune system. Blue modules in the WGCNA analysis were positively associated with the disease and were identified as key modules. ROC curves evaluated the four hub genes, which significantly differentiated RA from healthy controls and could be used as diagnostic biomarkers. In further analysis, we found that RA is closely related to immunity, and the search identified multiple drugs that hold promise for treating RA. CONCLUSIONS: BCL2A1, PTGS2, FAS, and LY96 may be used as diagnostic biomarkers, which is significant for diagnosing and treating RA.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Algoritmos , Ciclo-Oxigenase 2 , Bases de Dados Factuais
10.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(5): 732-735, 2023 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-37165820

RESUMO

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The ß value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The ß value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.


Assuntos
Vacinas contra Hepatite B , Hepatite B , Criança , Humanos , Lactente , Imunização Secundária , Antígenos de Superfície da Hepatite B , Memória Imunológica , Seguimentos , Vacinação , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B
11.
J Phys Chem C Nanomater Interfaces ; 127(20): 9896-9902, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37255927

RESUMO

Electrochemical charging of nanocrystal films opens up new possibilities for designing quantum dot-based device structures, but a solid theoretical framework of this process and its limitations is lacking. In this work, drift-diffusion simulations are employed to model the charging of nanocrystal films and gain insight into the electrochemical doping process. Through steady state simulations it is shown that the Fermi level and doping density in the nanocrystal film depend on the concentration of the electrolyte in addition to the value of the applied potential. Time-resolved simulations reveal that charging is often limited by transport of electrolyte ions. However, ion transport in the film is dominated by drift, rather than diffusion, and the concentration profile of ions differs substantially from concentration profiles of diffusing redox species at flat electrodes. Classical electrochemical theory cannot be used to model this type of mass transport limited behavior in films of nanocrystals, so a new model is developed. We show that the Randles-Sevcík equation, which is derived for electrochemical species diffusing in solution, but is often applied to films as well, results in a significant underestimation of the diffusion coefficients of the charge compensating electrolyte ions.

12.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 58(4): 380-385, 2023 Apr 09.
Artigo em Chinês | MEDLINE | ID: mdl-37005787

RESUMO

In the process of orthodontic tooth movement, the secretion of cytokines by immune cells or cell-cell interaction affects the regulation of osteoclast and osteoblast differentiation. Increasingly, studies have focused on the role in the immune system in orthodontic bone remodeling. Based on the biological role of different immune cells or cytokines, this article briefly presents the research progress of immunomodulation in orthodontic tooth movement and future perspective, hopefully providing a deeper and more comprehensive understanding of the biological mechanism in orthodontic tooth movement.

13.
Artigo em Chinês | MEDLINE | ID: mdl-37100752

RESUMO

Objective: To evaluate the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma (ACC), and to analyze the prognostic factors. Methods: Data of 82 patients (43 females and 39 males, at a median age of 49 years old) with sinonasal and skull base ACC who were admitted to XuanWu Hospital, Capital Medical University between June 2007 and June 2021 were analyzed retrospectively. The patients were staged according to American Joint Committee on Cancer (AJCC) 8th edition. The disease overall survival(OS) and disease-free survival(DFS) rates were calculated by Kaplan-Meier analysis. Cox regression model was used for multivariate prognostic analysis. Results: There were 4 patients with stage Ⅱ, 14 patients with stage Ⅲ, and 64 patients with stage Ⅳ. The treatment strategies included purely endoscopic surgery (n=42), endoscopic surgery plus radiotherapy (n=32) and endoscopic surgery plus radiochemotherapy (n=8). Followed up for 8 to 177 months, the 5-year OS and DFS rates was 63.0% and 51.6%, respectively. The 10-year OS and DFS rates was 51.2% and 31.8%, respectively. The multivariate Cox regression analysis showed that late T stage and internal carotid artery (ICA) involvement were the independent prognostic factors for survival in sinonasal and skull base ACC (all P<0.05). The OS of patients who received surgery or surgery plus radiotherapy was significantly higher than that of patients who received surgery plus radiochemotherapy (all P<0.05). Conclusions: Endoscopic transonasal surgery or combing with radiotherapy is an effective procedure for the treatment of sinonasal and skull base ACC. Late T stage and ICA involvement indicate poor prognosis.


Assuntos
Carcinoma Adenoide Cístico , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Adenoide Cístico/cirurgia , Estudos Retrospectivos , Base do Crânio/cirurgia , Base do Crânio/patologia , Intervalo Livre de Doença , Prognóstico
14.
Nature ; 614(7949): 682-687, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36813895

RESUMO

The invention of scanning probe microscopy revolutionized the way electronic phenomena are visualized1. Whereas present-day probes can access a variety of electronic properties at a single location in space2, a scanning microscope that can directly probe the quantum mechanical existence of an electron at several locations would provide direct access to key quantum properties of electronic systems, so far unreachable. Here, we demonstrate a conceptually new type of scanning probe microscope-the quantum twisting microscope (QTM)-capable of performing local interference experiments at its tip. The QTM is based on a unique van der Waals tip, allowing the creation of pristine two-dimensional junctions, which provide a multitude of coherently interfering paths for an electron to tunnel into a sample. With the addition of a continuously scanned twist angle between the tip and sample, this microscope probes electrons along a line in momentum space similar to how a scanning tunnelling microscope probes electrons along a line in real space. Through a series of experiments, we demonstrate room-temperature quantum coherence at the tip, study the twist angle evolution of twisted bilayer graphene, directly image the energy bands of monolayer and twisted bilayer graphene and, finally, apply large local pressures while visualizing the gradual flattening of the low-energy band of twisted bilayer graphene. The QTM opens the way for new classes of experiments on quantum materials.

15.
16.
Clin Radiol ; 78(2): e29-e36, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36192204

RESUMO

AIM: To established a radiomics nomogram for improving the dilatation and curettage (D&C) result in differentiating type II from type I endometrial cancer (EC) preoperatively. MATERIAL AND METHODS: EC patients (n=875) were enrolled retrospectively and divided randomly into a training cohort (n=437) and a test cohort (n=438), according to the ratio of 1:1. Radiomics signatures were extracted and selected from apparent diffusion coefficient (ADC) maps. A multivariate logistic regression analysis was used to identify the independent clinical risk factors. An ADC based-radiomics nomogram was built by integrating the selected radiomics signatures and the independent clinical risk factors. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) were calculated to compare the discrimination performances between the radiomics nomogram and the D&C result. RESULTS: Receiver operating characteristic (ROC) curves showed that the clinical risk factors, the D&C, and the ADC based-radiomics nomogram yielded areas under the ROC curves (AUCs) of 0.70 (95% CI: 0.64-0.76), 0.85 (95% CI: 0.80-0.89), and 0.93 (95% CI: 0.90-0.96) in the training cohort and 0.64 (95% CI: 0.57-0.71), 0.82 (95% CI: 0.77-0.87) and 0.91 (95% CI: 0.87-0.95) in the test cohort, respectively. The DCA, NRI, and IDI demonstrated the clinically usefulness of the ADC based-radiomics nomogram. CONCLUSION: The ADC-based radiomics nomogram could be used to improve the D&C result in differentiating type II from type I EC preoperatively.


Assuntos
Neoplasias do Endométrio , Nomogramas , Feminino , Humanos , Área Sob a Curva , Dilatação e Curetagem , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/cirurgia , Estudos Retrospectivos
18.
ACS Nano ; 16(12): 21216-21224, 2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36516407

RESUMO

We present a strategy to actively engineer long-range charge transport in colloidal quantum dot assemblies by using ligand functionalities that introduce electronic states and provide a path for carrier transfer. This is a shift away from the use of inactive spacers to modulate charge transport through the lowering of the tunneling barrier for interparticle carrier transfer. This is accomplished with the use of electronically coupled redox ligands by which a self-exchange chain reaction takes place and long-range charge transport is enabled across the film. We identified the different modes of charge transport in these quantum dot/redox ligand assemblies, their energetic position and kinetics, and explain how to rationally manipulate them through modulation of the Fermi level and redox ligand coverage.

19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(5): 884-895, 2022 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-36241231

RESUMO

OBJECTIVE: KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability. METHODS: In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5' rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We obtained a high-affinity TCR sequence that specifically recognized the HLA-A*11:01-restricted KRAS G12V8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability. CONCLUSION: KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.


Assuntos
Neoplasias , Proteínas Proto-Oncogênicas p21(ras) , Animais , DNA Complementar , Epitopos , Antígenos HLA-A , Humanos , Interferon gama , Camundongos , Camundongos Nus , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores de Antígenos de Linfócitos T/genética
20.
Phys Rev Lett ; 129(15): 156401, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36269973

RESUMO

Chiral materials have attracted significant research interests as they exhibit intriguing physical properties, such as chiral optical response, spin-momentum locking, and chiral induced spin selectivity. Recently, layered transition metal dichalcogenide 1T-TaS_{2} has been found to host a chiral charge density wave (CDW) order. Nevertheless, the physical consequences of the chiral order, for example, in electronic structures and the optical properties, are yet to be explored. Here, we report the spectroscopic visualization of an emergent chiral electronic band structure in the CDW phase, characterized by windmill-shaped Fermi surfaces. We uncover a remarkable chirality-dependent circularly polarized Raman response due to the salient in-plane chiral symmetry of CDW, although the ordinary circular dichroism vanishes. Chiral Fermi surfaces and anomalous Raman responses coincide with the CDW transition, proving their lattice origin. Our Letter paves a path to manipulate the chiral electronic and optical properties in two-dimensional materials and explore applications in polarization optics and spintronics.

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